Project Summary Obstructive sleep apnea (OSA) is a prevalent disorder with significant morbidity that has well-established adverse cardiovascular outcomes and increased mortality when left untreated. An emerging body of evidence suggests that untreated OSA may be associated with cancer but this association can be tested more rigorously in a large sample of OSA patients. We propose to test the association between OSA and cancer incidence and mortality in a cohort of over 1,000,000 veteran patients nationally through the Veteran's Affairs (VA) health system. We will carry out a retrospective cohort study of all VA patients with a diagnosis of OSA, as well as a control group of VA patients without OSA (>800,000) matched 4-to-1 for demographics, between 1991?2013 with up to 20 years of clinical follow up. We will further stratify patients based on those with untreated OSA (>200,000) and those that received treatment (>60,000) either with continuous positive airway pressure (CPAP) therapy or surgery. We will measure cancer incidence and cancer-related mortality and test the association with the presence or absence of pre-existing OSA, controlling for cancer risk factors and comorbidities. We hypothesize that patients with pre-existing OSA will have a higher incidence of cancer and higher cancer-related mortality than patients without pre-existing OSA. We also hypothesize that patients undergoing treatment for OSA will have reduced cancer incidence and cancer-related mortality than patients with pre-existing, untreated OSA. Our goal is to develop a better understanding of the burden of untreated OSA on cancer and the long-term impact of OSA treatment on cancer outcomes.